Neurotrophic factors are believed to be essential for normal neuronal function; in adequate provision of factors has been postulated to cause degenerative disease and the poor regeneration of CNS neuronal processes after trauma. Recent evidence suggests tha basic fibroblast growth factor (BFGF) is a trophic factor for many CNS neurons. It is also a mitogen for astrocytes and endothelial cells. Understanding its role in the CNS requires consideration of how it is shared among different cell types. Careful characterization of receptors found on different cell types is a logical point to begin this analysis. Initial studies suggest that there are differences between the BFGF receptors found on neurons and mesenchymal cells. More detailed examination might demonstrate dif- erences which could be exploited in designing a more neuron-specific analogue of BFGF. Initial studies show that most BFGF binds to glycosoaminoglycans (GAGs), with the remainder binding to two receptor proteins of 135 and 85 kD. In comparison to mesenchymal cells, neuronal bFGF receptors have 10-fold lower affinity. The 85 kD protein is found only on neurons. A panel of 13 peptide fragments of BFGF will be used to determine the domains interacting with the GAG and receptor sites. Comparing the results to mesenchymal cells will indicate whether the neuronal bFGF receptor has any distinct pharmacologc properties. Antibodies will be generated against the 135 and 85 kD proteins and used to determine whether they are distinct receptor molecules and for further comparison with mesenchymal cells. Possible regulation of the affinity of the receptor by phosphorylaion will be investigated. The molecules responsible for GAG-related BFGF binding will be defined; the two principal candidates are the heparan sulfate proteoglycan previously shown to bind laminin and the amyloid beta precursor protein related to Alzheimer's disease. The possibility that these GAG-related sites play a significant role in mediating biological responses to bFGF along with the receptors will be considered. A combination of peptide inhibitors, antibodies, lectins and heparin will be used to dissect out the roles of GAGS, the 135 kD and 85 kD receptors in biological responses to bFGF specifically neuronal survival and stimulation of neurite outgrowth. The role of GAG; receptors in internalization and degradation of BFGF will also be examined. Immunoistochemistry will be employed to clarify the relationships among BFGF and these binding sites on cultured neurons and in intact brain. Together these studies will clarify the mode of interaction between bFGF and CNS neurons.